Enantioselective Diels-Alder approach to C-3-oxygenated angucyclinones from...

Chiral racemic vinylcyclohexenes 2, bearing oxygenated substituents and/or a methyl group at the C-5 position of the cyclohexene ring, were submitted to Diels-Alder reactions with enantiomerically pure (SS)-(2-p-tolylsulfinyl)-1,4-naphthoquinone [(+)-1]. The domino cycloaddition/pyrolytic sulfoxide elimination process led to the formation of enantiomerically enriched angularly tetracyclic quinones anti-6 and syn-7, which were obtained from the kinetic resolution of the racemic diene. In all cases, (SS)-(2-p-tolylsulfinyl)-1,4-naphthoquinone reacted from the less hindered face of the more reactive s-cis conformation, to form products in good enantiomeric excesses. Steric effects and torsional interactions in the corresponding approaches account for the observed pi-facial diastereoselectivities at both partners. The usefulness of this methodology is illustrated with the four-step totally asymmetric synthesis of the C-3-oxygenated angucyclinone derivative (-)-8-deoxytetrangomycin 10 in 26% overall yield and with 50% enantiomeric purity.